Canadian Urological Association consensus guideline: Management of testicular germ cell cancer Flashcards
(281 cards)
1
Q
What is the most common solid malignancy in males aged 15-29?
A
Testicular cancer.
2
Q
What percentage of testicular cancers are primary germ cell tumors (GCTs)?
A
More than 90%.
3
Q
How are primary germ cell tumors of the testes histologically divided?
A
Into seminomas and non-seminomas (NSGCT).
4
Q
Which type of testicular GCT is rising at a faster rate?
A
Seminoma.
5
Q
What kind of approach does the management of testicular GCT require?
A
A multidisciplinary and coordinated approach.
6
Q
What potential benefits are there to GCT care being performed in, or coordinated with, experienced centers?
A
Improved survival, minimization of toxicity or overtreatment, experienced pathological review, specialist radiographic assessment, guideline-based recommendations, and timely delivery of multidisciplinary care.
7
Q
When was the Canadian consensus document on the management of testicular germ cell cancer last updated before 2018?
A
In 2010.
8
Q
What is the most common clinical presentation of germ cell tumors (GCTs)?
A
Most patients present with a palpable testicular mass that may or may not be painful.
9
Q
What is the primary tumor site in approximately 5% of GCT patients?
A
The primary tumor site is extragonadal (i.e., retroperitoneum or mediastinum).
10
Q
What diagnostic and staging examinations are mandatory for GCTs?
A
These include scrotal examination, determination of the serum tumor markers alpha-fetoprotein (AFP), ß-human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH), ultrasound to image the testicles, and a computed tomography (CT) scan of the thorax, abdomen, and pelvis.
11
Q
What is the initial diagnostic and treatment maneuver for GCTs, barring rare exceptions?
A
Radical orchiectomy performed through an inguinal incision, removing the testicle and spermatic cord to the level of the internal inguinal ring.
12
Q
When can orchiectomy be deferred in patients with GCTs?
A
Orchiectomy may be deferred in patients with life-threatening metastatic disease when a confirmed diagnosis of NSGCT (e.g., an unequivocally elevated AFP and/or HCG >5000 IU/L) or seminoma (e.g., biopsy of metastatic site) is made so as not to delay the start of chemotherapy. In such cases, orchiectomy should be performed after chemotherapy.
13
Q
When should tumor markers be drawn and repeated in patients with GCTs?
A
Tumor markers should be drawn prior to orchiectomy and repeated postoperatively within 1–3 weeks, and repeated to ensure return to normal, given the known half-life kinetics of AFP (<7 days) and ß-HCG (<3 days).
14
Q
What are the options if germ cell neoplasia in situ (GCNIS) is found in the remaining testicular tissue after organ-preserving surgery?
A
Options include completion orchiectomy, adjuvant radiotherapy, or surveillance, and discussion should include risk of cancer recurrence, hypogonadism, and fertility.
15
Q
What should the histopathological report document in the case of GCTs?
A
The report should document the procedure, specimen laterality, tumor focality, tumor size, tumor extension, histological type, margin status, presence or absence of lymphovascular invasion, number of lymph nodes involved and examined, pathology stage classification, and additional pathological findings. Mixed GCTs should have the estimated proportion of each component reported as a percentage (%).
16
Q
How should patients with metastatic disease be classified?
A
Patients with metastatic disease should be classified according to the International Germ Cell Cancer Collaborative Group (IGCCCG) classification system.
17
Q
What is a “burned out” primary in the context of advanced GCTs?
A
In advanced GCTs, the testicular primary tumor may spontaneously regress without treatment and at orchiectomy is described pathologically as a “burned out” primary.
18
Q
What are the mandatory investigations for managing testicular germ cell cancer according to the Canadian Urological Association consensus guideline?
A
The mandatory investigations include a complete history and physical exam (including a scrotal exam), laboratory tests (Alpha-fetoprotein (AFP), ß-human chorionic gonadotrophin (ß-HCG), Lactate dehydrogenase (LDH)), and baseline imaging (Scrotal ultrasound, CT abdomen and pelvis, CT thorax).
19
Q
What are the laboratory tests specified in the Canadian Urological Association consensus guideline for managing testicular germ cell cancer?
A
The laboratory tests specified are Alpha-fetoprotein (AFP), ß-human chorionic gonadotrophin (ß-HCG), and Lactate dehydrogenase (LDH).
20
Q
What baseline imaging procedures are recommended in the Canadian Urological Association consensus guideline for managing testicular germ cell cancer?
A
The recommended baseline imaging procedures are Scrotal ultrasound, CT of the abdomen and pelvis, and CT of the thorax.
21
Q
When are bone scans and brain imaging recommended in the management of testicular germ cell cancer?
A
Bone scans and brain imaging are recommended for patients with symptoms or poor prognosis metastatic disease.
22
Q
What is the International Germ Cell Cancer Collaborative Group’s classification for Non-Seminoma Germ Cell Tumor (NSGCT) with a “Good” prognosis?
A
NSGCT with a “Good” prognosis includes those with a testicular or retroperitoneal primary, no non-pulmonary visceral metastases, and good markers, specifically: AFP <1000 ug/L, ß-HCG <5000 IU/L, and LDH <1.5 × Upper Limit of Normal (ULN).
23
Q
What defines an “Intermediate” prognosis for NSGCT according to the International Germ Cell Cancer Collaborative Group’s classification?
A
NSGCT with an “Intermediate” prognosis includes those with a testicular or retroperitoneal primary, no non-pulmonary visceral metastases, and intermediate markers, specifically: AFP is between 1000 and 10,000 ug/L, or ß-HCG is between 5000 and 50,000 IU/L, or LDH is between 1.5 and 10 times the ULN.
24
Q
What criteria define a “Poor” prognosis for NSGCT as per the International Germ Cell Cancer Collaborative Group’s classification?
A
NSGCT with a “Poor” prognosis includes those with a mediastinal primary, and/or non-pulmonary visceral metastases, and/or any poor marker, specifically: AFP >10,000 ug/L, or ß-HCG >50,000 IU/L, or LDH >10 × ULN.
25
What is the International Germ Cell Cancer Collaborative Group's classification for a Seminoma with a "Good" prognosis?
Seminoma with a "Good" prognosis includes those with any primary site, no non-pulmonary visceral metastases, and normal AFP, regardless of ß-HCG and LDH levels.
26
What are the criteria for a Seminoma with an "Intermediate" prognosis according to the International Germ Cell Cancer Collaborative Group's classification?
Seminoma with an "Intermediate" prognosis includes those with any primary site, non-pulmonary visceral metastases, and normal AFP, regardless of ß-HCG and LDH levels.
27
When should tumor markers be drawn in the context of testicular germ cell cancer management?
Tumor markers should be drawn prior to orchiectomy and repeated postoperatively within 1–3 weeks. They should be rechecked until they return to normal, considering the known half-life kinetics of AFP (<7 days) and ß-HCG (<3 days).
28
What is the recommended procedure in rare cases where there's a possibility of a benign tumor?
In such cases, an excisional biopsy with a frozen section should be performed prior to definitive orchiectomy in an experienced center. This allows for the possibility of organ-sparing partial orchiectomy.
29
In which patients may partial orchiectomy be an alternative procedure to orchiectomy?
Partial orchiectomy may be an alternative in patients with synchronous bilateral tumors, metachronous contralateral tumors, or solitary testicles with normal preoperative testosterone levels. This procedure should be performed by an experienced surgeon.
30
What options are available if organ-preserving surgery is performed and germ cell neoplasia in situ (GCNIS) is found in the remaining testicular tissue?
Options include completion orchiectomy, adjuvant radiotherapy, or surveillance. The discussion should include the risk of cancer recurrence, hypogonadism, and fertility.
31
What should always be discussed with all patients undergoing therapy for germ cell tumors (GCT)?
A full discussion on semen cryo-preservation should take place for all patients undergoing therapy (surgery, chemotherapy, and/or radiation) for GCT.
32
What points should the histopathological report document?
The report should document the procedure, specimen laterality, tumor focality, tumor size, tumor extension, histological type, margin status, presence or absence of lymphovascular invasion, number of lymph nodes involved and examined, pathology stage classification, and additional pathological findings. For mixed GCTs, the estimated proportion of each component should be reported as a percentage. Immunohistochemistry is considered a useful adjunct to the diagnosis of testicular tumors.
33
Who should assess testicular tumors?
Testicular tumors should be assessed by a pathologist experienced in testis cancer pathology.
34
How should patients with metastatic disease be classified?
Patients with metastatic disease should be classified according to the IGCCCG classification system.
35
What are the requirements for a Clinical Stage I (CSI) seminoma?
A CSI seminoma requires:
An orchiectomy specimen containing pure seminoma only
Normalized markers post-orchiectomy
No history of an elevated AFP
Normal staging imaging
36
What is the risk of relapse in Clinical Stage I (CSI) seminoma cases, and where does it most commonly occur?
The risk of relapse in Clinical Stage I (CSI) seminoma cases is 15%, with most occurring in the retroperitoneum.
37
What are the treatment options for Clinical Stage I (CSI) seminoma?
Treatment options for Clinical Stage I (CSI) seminoma include:
Surveillance
Para-aortic ± pelvic radiotherapy
Chemotherapy (carboplatin x 1–2)
38
Why is surveillance the preferred approach for all Clinical Stage I (CSI) seminoma patients?
Surveillance is the preferred approach for all Clinical Stage I (CSI) seminoma patients because adjuvant treatment is associated with acute toxicities, the risk of late side effects, potential overtreatment in 85% of cases, and no improvement in survival.
39
What is important to consider when deciding the treatment for Clinical Stage I (CSI) seminoma patients?
All patients should have a shared discussion balancing the risk of relapse and the side effects of adjuvant treatment.
40
What is the range of relapse rates at five years for CSI seminoma based on non-randomized studies of surveillance?
The relapse rates at five years range from 11–20%.
41
What is the predominant site of relapse for CSI seminoma?
The predominant site of relapse is the para-aortic lymph nodes.
42
What is the median time to relapse in CSI seminoma and can late relapses occur?
The median time to relapse is 12–18 months, but late relapses (>4 years) have been reported.
43
What risk factors have been associated with relapse in CSI seminoma?
Tumor size >4 cm and rete testes involvement have been associated with relapse, although these risk factors have shown inconsistent results across studies.
44
What is the proposed risk-adapted strategy for managing CSI seminoma?
The Spanish Germ Cell Cancer Cooperative Study Group and the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) have proposed a risk-adapted strategy with surveillance for low-risk patients (0 risk factors) and adjuvant therapy for high-risk patients (1–2 risk factors).
45
What is the potential concern with non-risk-adapted surveillance in CSI seminoma?
The potential concern is the increased use of chemotherapy to salvage patients who relapse.
46
What is the effectiveness of radiotherapy as a sole salvage approach in CSI seminoma?
Most relapses occur in the retroperitoneum, where radiotherapy has proven to be an effective sole salvage approach.
47
What are the current debates in optimal follow-up surveillance strategy in CSI seminoma?
There is ongoing debate about the contribution of serial tumor marker assessments, the efficacy of MRI imaging compared to CT scans, and the number of scans in a surveillance schedule.
48
What is the role of adjuvant retroperitoneal radiotherapy in the management of testicular germ cell cancer?
Adjuvant retroperitoneal radiotherapy is limited to occasional circumstances where surveillance is not feasible.
49
Adjuvant retroperitoneal radiotherapy is limited to occasional circumstances where surveillance is not feasible.
The reported relapse rate is 4% (range 0.8–5%).
50
How common is relapse >3 years after radiotherapy in the treatment of testicular germ cell cancer?
Relapse >3 years after radiotherapy appears rare, occurring in only three of 1893 patients entered onto the MRC TE10, TE18, and TE19 adjuvant trials.
51
What does evidence from randomized trials say about the relapse rates for para-aortic nodal radiotherapy vs. extended volume to include ipsilateral pelvic nodes?
Evidence from randomized trials demonstrates similar overall relapse rates for para-aortic nodal radiotherapy vs. extended volume to include ipsilateral pelvic nodes (3.4% vs. 4%).
52
What is the recommendation for patients who didn't have their pelvic recurrence included in the initial treatment volume?
Continued imaging to detect pelvic recurrence is recommended if this was not included in the initial treatment volume.
53
What are the three treatment options listed in the Canadian Urological Association consensus guideline for managing Clinical Stage I seminoma?
The three treatment options are Surveillance, Carboplatin x 1, and Radiation.
54
According to the Canadian Urological Association consensus guideline, what is the relapse rate when using Surveillance as a treatment option for Clinical Stage I seminoma?
The relapse rate for Surveillance is 15%.
55
What is the relapse rate for Clinical Stage I seminoma when treated with a single round of Carboplatin, as per the Canadian Urological Association consensus guideline?
The relapse rate for a single round of Carboplatin treatment is 5%.
56
Based on the Canadian Urological Association consensus guideline, what is the relapse rate when Radiation is used as a treatment option for Clinical Stage I seminoma?
The relapse rate for Radiation treatment is 4%.
57
What is the cancer-specific survival rate for all three treatment options (Surveillance, Carboplatin x 1, Radiation) for Clinical Stage I seminoma according to the Canadian Urological Association consensus guideline?
The cancer-specific survival rate for all three treatment options is 99%.
58
What is the role of adjuvant chemotherapy in the management of testicular germ cell cancer according to the Canadian Urological Association consensus guideline?
Adjuvant chemotherapy is limited to occasional circumstances where surveillance is not feasible.
59
What are the recommended cycles of carboplatin for adjuvant chemotherapy in the management of testicular germ cell cancer?
1-2 cycles of carboplatin are options, but it remains unclear whether one or two cycles are better.
60
What were the five-year relapse rates in the MRC TE19 study comparing adjuvant radiotherapy to one cycle of carboplatin in testicular germ cell cancer patients?
The five-year relapse rates were similar: 4.0% for adjuvant radiotherapy and 5.3% for one cycle of carboplatin.
61
According to non-randomized data, how does the number of carboplatin cycles affect the relapse rates in testicular germ cell cancer patients?
Non-randomized data suggest a reduction in relapses with two cycles of carboplatin (1.5-3% relapse rate) compared to one cycle (5% relapse rate).
62
What does the SWENOTECA data show regarding the relapse rates in lower-risk and higher-risk patients given one cycle of carboplatin compared to surveillance?
The SWENOTECA data shows a small risk reduction with one cycle of carboplatin compared to surveillance: 2.2% vs. 4.0% relapse rate in lower-risk patients and 9.3% vs. 15.5% relapse rate in higher-risk patients.
63
What are the potential disadvantages of adjuvant chemotherapy with carboplatin in the management of testicular germ cell cancer?
The reduction in relapse risk is not substantial (15% to 5%), most relapses occur in the retroperitoneum requiring CT scans similar to surveillance, recurrence after carboplatin may have worse biology, and long-term toxicity of carboplatin is unknown.
64
What are the implications of recurrence after carboplatin therapy in the management of testicular germ cell cancer?
Recurrence after carboplatin may result in a higher burden of disease at relapse, greater reliance on BEP as salvage, and a greater incidence of second relapse and death.
65
How are patients with rising tumor markers after orchiectomy, despite normal imaging, classified, and how should they be treated?
These patients are considered stage IS and should be treated with chemotherapy according to the corresponding IGCCCG group.
66
What is the recommended approach to discussing treatment options with patients?
Patients should be informed of all treatment options, including surveillance, adjuvant chemotherapy, adjuvant radiotherapy, and the potential benefits and side effects of each treatment. They should be involved in the decision-making process.
67
What is the preferred treatment option for a patient willing and able to adhere to a surveillance program?
Surveillance should be the preferred option.
68
Is a risk-adapted approach with surveillance for low-risk patients and adjuvant treatment for those at higher risk of relapse recommended?
No, a risk-adapted approach like this is not recommended.
69
What are the potential adjuvant therapies for testicular germ cell cancer?
If adjuvant therapy is chosen, carboplatin chemotherapy and radiation therapy are options.
70
If adjuvant therapy is given, is post-therapy imaging still required?
Yes, post-therapy imaging is still required, similar to surveillance schedules.
71
Is there a role for primary retroperitoneal lymph node dissection (RPLND) in stage I seminoma?
At present, there is no role for primary RPLND in stage I seminoma.
72
What is the recommended initial approach for patients with CSIIA seminoma without marker elevation?
An initial period of surveillance with repeat imaging in 6–8 weeks, as up to 30% of cases end up being false-positive nodal enlargement.
73
What are the treatment options for CSIIA seminoma?
Radiotherapy or chemotherapy. Note, there has been no randomized trial comparing these two options in this setting.
74
What is the outcome of radiation therapy in CSIIA seminoma?
Radiation therapy to the para-aortic and ipsilateral pelvic nodes with doses ranging from 30–35 Gy yields five-year relapse-free rates in excess of 90% in most modern series.
75
What are the treatment options for CSIIB seminoma?
Radiation therapy or chemotherapy, depending on the bulk of the disease and location of lymph nodes.
76
How do chemotherapy and radiation therapy perform in CSIIB disease according to meta-analysis?
They achieve similar disease control in CSIIA disease, but chemotherapy does modestly better in CSIIB disease (relapse rate 5% vs. 12%), with a lower incidence of late toxicity and secondary cancers.
77
What is the recommended treatment for CSIIC seminoma?
Chemotherapy. The relapse rate with radiation therapy approaches 50% in most series, and not all patients can be salvaged with chemotherapy.
78
What is the recommended chemotherapy for all CSII seminoma patients?
The same as that for IGCCCG good-prognosis patients.
79
What is the role of RPLND and reduced volume radiation therapy in combination with a single course of carboplatin in CSII seminoma?
It is the subject of clinical trials and not an established option outside of a trial setting.
80
What is the classification for non-seminomatous germ cell testicular cancer (NSGCT)?
Testicular cancer is classified as NSGCT if, histologically, the tumor contains any component of embryonal carcinoma, yolk sac tumor, choriocarcinoma, or teratoma. Also, patients with histologically pure seminoma but elevated serum AFP or markedly elevated HCG (generally regarded as >5000 IU/L) are considered to have NSGCT.
81
How is stage IS NSGCT defined and treated?
Patients with persistently elevated or rising markers 4–6 weeks after orchiectomy with normal imaging are considered stage IS NSGCT. They should be treated with chemotherapy according to their corresponding IGCCCG group.
82
What are the treatment options for Clinical Stage I (CSI) NSGCT?
Treatment options for CSI NSGCT include surveillance, chemotherapy (typically BEP x 1–2), or retroperitoneal lymph node dissection (RPLND).
83
What percentage of stage I NSGCT patients relapse without adjuvant treatment?
Approximately 20–30% of stage I NSGCT patients relapse without adjuvant treatment.
84
What is the preferred treatment approach for all CSI NSGCT patients?
Surveillance is the preferred treatment approach for all CSI NSGCT patients.
85
What are the risk factors associated with increased relapse in NSGCT patients?
The main risk factor associated with increased relapse is the presence of lympho-vascular invasion (LVI) in the orchiectomy specimen, which upstages NSGCT from pT1 to pT2 and overall CSIA to CSIB. Some data also show that embryonal predominance is associated with relapse, with the cutoff for defining embryonal predominance varying in the published series from >50% to 100%.
86
What is the associated risk of relapse if lympho-vascular invasion (LVI), embryonal predominance, or both are present in NSGCT patients?
If LVI, embryonal predominance, or both are present, the associated risk of relapse is approximately 50%.
87
What are the main risk factors in CSI patients that increase the relapse rate up to 50%?
Lymphovascular invasion (LVI) and embryonal predominance.
88
What percentage of patients on surveillance do not require any further therapy after orchiectomy?
74%
89
What is the traditional treatment method for patients who relapse during surveillance?
3-4 cycles of chemotherapy.
90
What is an argument against surveillance for high-risk CSI NSGCT?
The higher treatment burden for the 50% who experience a relapse compared to a strategy of upfront adjuvant therapy.
91
What is a recently demonstrated safe method for salvaging CSI NSGCT surveillance relapses?
Retroperitoneal lymph node dissection (RPLND).
92
What percentage of patients treated with RPLND did not require any subsequent chemotherapy?
73%
93
How does the chemotherapy burden of high-risk patients treated with surveillance and salvaged with RPLND compare to those treated with adjuvant BEPx1?
It's similar. In a model, a theoretical cohort of 100 high-risk patients treated with surveillance and salvaged preferentially with RPLND had a similar chemotherapy burden to a group treated with adjuvant BEPx1.
94
What is the recurrence rate observed in non-randomized trials and a single randomized trial using adjuvant chemotherapy in CSI NSGCT?
The recurrence rate using a variety of platinum-based regimens is 3.8%.
95
What was the recurrence rate in high-risk patients treated with two cycles of BEP chemotherapy?
The relapse rate after two cycles of BEP chemotherapy ranged from 2.2–2.9%.
96
What was the relapse rate in the study by the SWENOTECA group comparing surveillance vs. BEP x1 in patients with Lymphovascular Invasion (LVI)?
In patients with LVI, 41.7% of patients on surveillance relapsed compared to 3.2% receiving BEP x1.
97
What was the 5-year cause-specific survival rate for the chemotherapy arm in the SWENOTECA group study?
The 5-year cause-specific survival was 100% for the chemotherapy arm, with no treatment-related mortality.
98
What were the results of the U.K. single-arm "111 Study" on the efficacy of BEP x1 in CSIB NSGCT?
The U.K. "111 Study" confirmed the efficacy of BEP x1 in CSIB NSGCT with a 3.1% relapse rate and one death with 49-month median follow-up.
99
Why is shared decision-making critical when considering adjuvant chemotherapy for testicular germ cell cancer?
Shared decision-making is critical due to limited information on very long-term follow-up (>20 years) relating to complications such as cardiovascular health after BEP x 1–2 treatment.
100
What are the treatment options for stage I non-seminomatous germ cell tumor (NSGCT)?
The treatment options for stage I NSGCT are surveillance, BEPx1 (a cycle of bleomycin, etoposide, and cisplatin), and retroperitoneal lymph node dissection (RPLND).
101
What is the relapse rate for NSGCT under surveillance?
The relapse rate for NSGCT under surveillance is 26%.
102
What is the relapse rate for NSGCT with a treatment of BEPx1?
The relapse rate for NSGCT with a treatment of BEPx1 is between 2% and 7%.
103
What is the relapse rate for NSGCT with a treatment of RPLND?
The relapse rate for NSGCT with a treatment of RPLND is 10%.
104
What is the cancer-specific survival rate for NSGCT under surveillance, BEPx1 treatment, and RPLND treatment?
The cancer-specific survival rate for NSGCT under surveillance, BEPx1 treatment, and RPLND treatment is 99%.
105
What does the 10% relapse rate for RPLND treatment of NSGCT include?
The 10% relapse rate for RPLND treatment of NSGCT includes giving adjuvant chemotherapy to select patients with positive nodes at RPLND.
106
What is a significant drawback of studies regarding adjuvant RPLND?
Most studies give two cycles of chemotherapy to patients with pathological nodal disease, making it unclear to determine the sole benefits of RPLND when compared to BEPx1 as upfront adjuvant therapy for high-risk CSI NSGCT.
107
What was the relapse rate difference between RPLND and BEPx1, according to the only randomized trial comparing them?
The relapse rate was significantly higher for RPLND (8%) compared to BEPx1 (0.5%).
108
How many patients who received RPLND had pathological stage II disease at surgery and received BEPx2? What was the relapse rate for these patients?
18.5% of the patients who received RPLND had pathological stage II disease at surgery and received BEPx2. No relapses were observed in these patients.
109
How many recurrences were observed in patients managed with RPLND alone?
13 recurrences were observed, seven of which were in the retroperitoneum.
110
What is one highlighted finding from the criticized trial that compared RPLND to BEPx1?
The trial highlighted that if RPLND is to be completed, it should be done at high-volume centers.
111
What does the retrospective series data tell us about the relapse and mortality rates post-RPLND?
About 10% relapse post-RPLND and less than 1% die of the disease.
112
What percentage of patients with pathological nodal disease found at RPLND, who do not receive adjuvant chemotherapy, relapse?
Approximately 20% of patients with pathological nodal disease found at RPLND, who do not receive adjuvant chemotherapy, relapse.
113
What are the advantages of RPLND?
RPLND provides the most accurate staging, 80-90% of patients can avoid the potential long-term side effects of chemotherapy, and it allows for surgical excision of chemo-resistant teratoma.
114
What are the long-term complications of RPLND?
Long-term complications of RPLND can include loss of antegrade ejaculation, ventral hernia, and bowel obstruction. However, these are rare if performed in centers of excellence.
115
What is the stance on RPLND as an adjuvant treatment option?
Despite its decreasing use over time, RPLND remains an acceptable option in the properly selected and informed individual for adjuvant treatment.
116
What is guideline i in the 'Management of testicular germ cell cancer' according to the Canadian Urological Association?
Patients with rising tumor markers after orchiectomy despite normal imaging are considered stage IS and should be treated with chemotherapy according to the corresponding IGCCCG group.
117
What is guideline ii in the 'Management of testicular germ cell cancer' according to the Canadian Urological Association?
Patients should be informed of all treatment options (surveillance, adjuvant chemotherapy, RPLND), including the potential benefits and side effects of each treatment, and should be involved in the decision-making process.
118
What is guideline iii in the 'Management of testicular germ cell cancer' according to the Canadian Urological Association?
In a patient willing and able to adhere to a surveillance program, for all stage I risk groups, surveillance should be the preferred option.
119
What is guideline iv in the 'Management of testicular germ cell cancer' according to the Canadian Urological Association?
For patients who prefer immediate treatment or who are unsuitable for primary surveillance, adjuvant chemotherapy or RPLND are both options.
120
What is guideline v in the 'Management of testicular germ cell cancer' according to the Canadian Urological Association?
If adjuvant chemotherapy is chosen, one cycle of BEP is the preferred option.
121
What is guideline vi in the 'Management of testicular germ cell cancer' according to the Canadian Urological Association?
If RPLND is chosen, surgery should be performed by surgeons who are experienced with the procedure. Full bilateral templates and nerve-sparing techniques should be employed.
122
What is the cure rate for Clinical Stage IIA and IIB Nonseminomatous Germ Cell Tumors (NSGCT)?
The cure rate approaches 98%.
123
What are the three management options for CS IIA NSGCT patients without marker elevation?
Surveillance, primary Retroperitoneal Lymph Node Dissection (RPLND), or chemotherapy.
124
What approach is recommended for most CS IIA NSGCT patients and how should the situation be evaluated over time?
Initial surveillance is recommended with repeat imaging after 6-8 weeks to determine lesion change. A shrinking lesion is likely not malignant and should continue to be observed. A stable or growing lesion may indicate teratoma or malignant tumor and a primary RPLND can be both diagnostic and therapeutic.
125
What is the main consideration for patients with a rapidly growing lesion and/or increased markers?
Patients should be treated with primary chemotherapy according to the International Germ Cell Cancer Collaborative Group (IGCCCG).
126
For confirmed CS IIA or B NSGCT patients, what are the two treatment options and how might the course of treatment evolve?
The two options are primary RPLND or primary chemotherapy. If RPLND is performed, adjuvant chemotherapy may be offered if viable germ cell elements are found in the pathology. If chemotherapy is initiated, a post-chemotherapy RPLND may be required if residual disease >1 cm is seen on post-chemotherapy imaging.
127
What are the relapse rates for patients with pathological stage IIA and IIB disease who underwent primary RPLND alone?
The relapse rates are 10% for stage IIA and 35-50% for stage IIB.
128
What is the benefit and potential downside of primary RPLND followed by adjuvant chemotherapy with BEPx2?
It reduces the relapse risk to approximately 1% but it may be overtreatment in 50-70% of patients.
129
What is the complete response rate in patients treated with primary chemotherapy with BEPx3 or four cycles of etoposide and cisplatin (EP)?
The response rate is 83-91% in patients with clinical stage IIA and 61-87% in patients with clinical stage IIB.
130
What is the complete response rate in patients treated with primary chemotherapy with BEPx3 or four cycles of etoposide and cisplatin (EP)?
It might be an option for patients wishing to avoid chemotherapy and willing to accept a higher relapse risk with RPLND alone.
131
What is the recommended surgical approach when performing RPLND?
A full bilateral template with nerve-sparing technique should be used, preferably at centers with experience in performing this operation.
132
Figure 1. Clinical stage IIA/IIB non-seminomatous germ cell tumor treatment algorithm. PCRPLND: post-chemotherapy retroperitoneal lymph node dissection.
133
What is the recommended initial approach for patients with stage IIA testicular germ cell cancer without marker elevation?
An initial period of surveillance with repeat imaging in 6–8 weeks.
134
What is the preferred approach for patients with confirmed stage IIA testicular germ cell cancer and negative markers?
Primary RPLND is the preferred approach, but primary chemotherapy is also an acceptable option.
135
What is the preferred treatment option for patients with stage IIA testicular germ cell cancer and positive tumor markers?
Primary chemotherapy according to the IGCCCG recommendation is the preferred option. RPLND remains an option in select patients with low-level and slowly rising markers who wish to avoid chemotherapy, though a higher relapse risk is acknowledged.
136
What is the recommended treatment for patients with stage IIB testicular germ cell cancer, regardless of marker status?
Primary chemotherapy according to the IGCCCG criteria is the recommended treatment. RPLND may be an option in highly select patients, though a higher relapse risk is acknowledged.
137
What are the recommendations if RPLND is chosen as the treatment method?
Surgery should be performed by surgeons who are experienced with the procedure. Full bilateral templates and nerve-sparing techniques should be employed.
138
When is the routine use of granulocyte colony-stimulating factor (G-CSF) for primary prophylaxis recommended?
Routine use of G-CSF for primary prophylaxis is not recommended in all patients. However, it should be considered for intermediate- and poor-risk patients, or those at high risk based on age, comorbidities, and disease characteristics. Patients receiving ifosfamide must receive primary prophylaxis.
139
"How often should chemotherapy be given for advanced or metastatic germ cell cancer, and should dose reductions be considered based on the neutrophil count on day 1?"
"Chemotherapy should be given without dose reductions at 21-day intervals, regardless of the neutrophil count on day 1."
140
Why shouldn't Carboplatin be substituted for Cisplatin?
Carboplatin should not be substituted for Cisplatin in the treatment of advanced germ cell tumors due to inferior outcomes.
141
When should secondary prophylaxis be considered in the treatment of advanced or metastatic germ cell cancer?"
"Secondary prophylaxis should be considered for patients with prior infectious or neutropenic complications."
142
What is the recommended treatment protocol for patients with advanced germ cell tumors (GCTs)?
Patients with advanced GCTs should always be considered curable and must be referred to an experienced center for consultation. They should be stratified into a prognostic group using the IGCCCG criteria based on histology, site of primary, and degree of post-orchiectomy tumor marker elevation (AFP, β-HCG, and LDH). Standard chemotherapy for most patients is BEP given over five days every 21 days.
143
What is the IGCCCG criteria?
The IGCCCG criteria is used to stratify patients with advanced germ cell tumors into prognostic groups based on histology, site of primary, and degree of post-orchiectomy tumor marker elevation (AFP, β-HCG, and LDH).
144
What are the standard chemotherapy drugs for advanced GCTs?
The standard chemotherapy for advanced germ cell tumors is BEP (Bleomycin, Etoposide, Cisplatin) given over five days every 21 days.
145
What is the preferred treatment option for patients with good-prognosis disease?
For patients with IGCCCG good-prognosis disease, BEPx3 is the preferred option. If there is a contraindication to bleomycin , EPx4 can be given, but it has been associated with a non-statistically significant but higher death rate.
146
How should patients with intermediate or poor-prognosis disease be treated?
Patients with intermediate or poor-prognosis disease should be considered oncological emergencies and treated urgently with BEPx4 as the standard therapy. Even brief treatment delays should be avoided, as these tumors can progress rapidly. VIP represents an alternative to BEP for patients with contraindications to bleomycin.
147
When is the use of the VIP chemotherapy regimen recommended?
VIP (Etoposide, Cisplatin, Ifosfamide) should be considered for patients with extensive pulmonary disease, a mediastinal primary, and/or brain metastases, or if they develop pulmonary toxicity during BEP.
148
How should chemotherapy be administered?
Chemotherapy should be given without dose reductions at 21-day intervals regardless of the neutrophil count on day 1. Routine use of granulocyte colony-stimulating factor (G-CSF) for primary prophylaxis is not recommended in all patients.
149
What are the implications of LDH elevation alone for IGCCCG classification?
LDH elevation alone for IGCCCG classification is controversial and these cases should be discussed with oncologists in experienced centers.
150
What is the effect of using BEP chemotherapy on a three-day schedule?
Using BEP chemotherapy on a three-day schedule has been found to have equivalent efficacy to the same drugs given over a five-day schedule, but has less short-term gastrointestinal toxicity and long-term ototoxicity.
151
What is the importance of monitoring tumor markers in managing testicular germ cell cancer during chemotherapy?
Tumor markers need to be monitored prior to each chemotherapy cycle. They help to track the progress of the treatment and detect any anomalies.
152
When could radiological imaging be useful during chemotherapy, even though it's not mandatory?
Radiological imaging may be useful in patients with no elevated tumor markers, a significant amount of teratoma in the primary, large retroperitoneal masses, or new/progressive symptoms.
153
What is the potential risk for patients with GCTs undergoing chemotherapy? What preventive measures can be taken?
These patients are at an increased risk for vascular thromboembolic events (VTEs). Prophylactic anticoagulation with low molecular weight heparins or Factor X inhibitors can reduce this risk, although it slightly increases the risk of bleeding.
154
What factors should be considered when deciding to use prophylactic anticoagulation in patients with GCTs undergoing chemotherapy?
Factors to consider include increased tumor bulk, retroperitoneal lymph nodes >3.5 cm, stage, chemotherapy exposure, Khorana score ≥3, and the presence of vascular access devices.
155
What is bleomycin-related pneumonitis and how is it managed in patients undergoing BEP therapy?
Bleomycin-related pneumonitis is a rare but known complication of BEP therapy. The risk increases with bleomycin exposure and age. Monitoring of symptoms is important, as PFTs during treatment are not useful for early identification of pneumonitis. In case of pneumonitis of clinical concern, bleomycin should be discontinued and an alternative chemotherapy regimen with similar therapeutic dose intensity should be completed.
156
What is considered a poor prognostic factor in patients with poor-prognosis NSGCT?
A suboptimal decline in AFP and/or β-HCG after the first cycle of BEP is considered a poor prognostic factor.
157
What actions should be taken if there is an unequivocal rise in AFP and/or β-HCG tumor markers?
Radiological imaging is required, including imaging of the brain. If there's radiological progression, a switch to salvage chemotherapy may be necessary and the patient must be referred to an experienced center.
158
When should post-chemotherapy radiological restaging be performed?
Radiological restaging should be performed in all patients 4–8 weeks after day 21 of the last chemotherapy cycle.
159
How should patients with a markedly elevated β-HCG prior to treatment be managed?
A delay in normalization of β-HCG is not uncommon. Unless tumor markers are rising, all residual masses should be treated as per the sections below.
160
What are the possible histologies of residual masses after first-line chemotherapy for NSGCT?
The possible histologies are necrosis (40-50%), teratoma (35-40%), and viable cancer (10-15%). The incidence of viable cancer is declining in more recent series and may be as low as 6%.
161
What are some factors associated with the absence of a viable tumor in the residual mass of NSGCT post-chemotherapy?
The factors include absence of teratoma in the primary tumor, normal markers pre-chemotherapy, a small pre-chemotherapy mass, significant shrinkage of the mass with chemotherapy, and size of residual mass ≤10 mm.
162
When should PC-RPLND be considered in the management of post-chemotherapy NSGCT patients?
PC-RPLND should be considered in patients with normal tumor markers and residual retroperitoneal masses ≥1 cm in dimension. It can also be indicated in select cases with low-level but stable marker elevations.
163
How should masses <1 cm be managed in post-chemotherapy NSGCT patients?
For masses <1 cm, surveillance is the preferred option, with several large series demonstrating relapse rates of 6–9%.
164
What is the preferred surgical approach in the post-chemotherapy setting of NSGCT and why?
The preferred approach is bilateral RPLND with nerve-sparing, when feasible. This approach is preferred to minimize complications and the risk of leaving residual disease.
165
What is the recommended timeframe for performing surgery post-chemotherapy in NSGCT patients?
Most centers advocate performing surgery within 12 weeks after completing chemotherapy. However, in cases of good-risk disease, negative markers, and shrinking masses, or in patients with chemotherapy complications, a delay may be appropriate.
166
What factors impact the prognosis in post-chemotherapy NSGCT patients?
Complete resection of the residual masses impacts prognosis and every attempt at complete surgical resection must be made. Increasingly, data supports a relationship between lymph node yield, hospital surgical volume, and improved outcomes.
167
How should residual masses outside the retroperitoneum be managed in post-chemotherapy NSGCT patients?
Resection of residual masses outside the retroperitoneum must also be considered. In most cases, the retroperitoneum should be operated on first. However, concomitant resections involving retrocrural, mediastinal, hepatic, thoracic, and supraclavicular disease have been described with acceptable morbidity.
168
What is the concordance in pathology between the retroperitoneum and other metastatic sites in NSGCT?
The concordance in the pathology between the retroperitoneum and other metastatic sites ranges from 50–89%. Thus, surgeons should maintain a low threshold to resect extra-retroperitoneal disease due to the imperfect concordance.
169
What is the recommended management for post-chemotherapy residual masses in advanced seminoma less than 3 cm?
These patients can be safely surveyed. The use of FDG-PET scanning is not recommended.
170
How should post-chemotherapy residual masses in advanced seminoma equal to or greater than 3 cm be managed?
An FDG-PET scan may be considered, but its clinical relevance is debated. A negative FDG-PET scan is useful in predicting necrosis, and surveillance is the standard of care. A positive FDG-PET scan needs to be interpreted cautiously and does not automatically lead to immediate treatment. Continued close observation is often the preferred option.
171
When is it appropriate to consider surgical resection or biopsy for post-chemotherapy residual masses in advanced seminoma?
Surgical resection or biopsy is considered when the FDG-PET scan remains strongly positive over time or there is a high suspicion of viable disease. These procedures should only be performed at an experienced centre.
172
What are the advantages and disadvantages of surgery for post-chemotherapy residual masses in advanced seminoma?
The advantages of surgery include the ability to assess the chemotherapy response, obtain histology, and potentially provide a cure. The disadvantage is the high morbidity, as complete resection is challenging due to the intense desmoplastic reaction when seminoma is treated with chemotherapy.
173
What is the usual extent of surgical resection in post-chemotherapy residual masses in advanced seminoma?
The extent of surgical resection in seminoma is usually a resection of the residual mass or multiple biopsies, and it does not usually include a full or modified RPLND.
174
What is the role of radiation therapy in the management of post-chemotherapy residual masses in advanced seminoma?
Radiation therapy may be given in select cases, however, identifying those who may benefit remains challenging, as this has been inadequately studied.
175
What are the guidelines for further treatment after completely resected residual masses in testicular germ cell cancer?
If the pathology shows necrosis or mature teratoma, no further treatment is required. If viable cancer is found, the need for further chemotherapy is unclear due to a lack of prospective data. A discussion with the treating surgeon is necessary to understand the extent of dissection and any concern for residual unresected disease.
176
According to retrospective data, does consolidation chemotherapy improve overall survival (OS) in testicular germ cell cancer?
No, retrospective data have shown that while consolidation chemotherapy can improve disease-free survival, it does not significantly impact overall survival.
177
What are the three independent predictive factors for improved progression-free and overall survival in testicular germ cell cancer?
The three independent predictive factors are complete surgical resection, less than 10% viable malignant cells, and a good IGCCCG prognostic group.
178
What is the general approach if post-surgery chemotherapy is given in cases of testicular germ cell cancer?
No specific chemotherapy regimen or number of cycles can be universally recommended. However, most oncologists would choose two cycles of a different regimen, considering that viable cells may represent at least partial chemoresistance. If the viable cells indicate a transformation, such as to sarcoma or adenocarcinoma, chemotherapy specific to that histological subtype should be chosen.
179
In what percentage of patients with metastatic Germ Cell Tumors (GCT) do brain metastases occur at presentation?
Brain metastases occur in only 2-3% of patients with metastatic GCT at presentation.
180
What histology is most common in patients with brain metastases from GCT?
Greater than 95% of brain metastases from GCT are Non-Seminomatous Germ Cell Tumors (NSGCT) histology.
181
How does the survival rate differ between patients with synchronous brain metastases at initial diagnosis and those who develop metachronous disease?
Patients with synchronous brain metastases at initial diagnosis have a three-year Overall Survival (OS) of 48%, compared to a 27% OS for patients who develop metachronous disease.
182
Why is VIP chemotherapy preferred for patients with brain metastases from GCT?
VIP chemotherapy is preferred as ifosfamide, a component of the regimen, can cross the blood-brain barrier, whereas bleomycin cannot.
183
What factors dictate prognosis in patients with brain metastases from GCT?
Prognosis is dictated by International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic factors and may be influenced by the number of brain metastases.
184
What is the stance on local treatment of post-chemotherapy residual masses in the brain?
Local treatment of post-chemotherapy residual masses in the brain with radiation therapy or surgery may be considered, but the routine use of multimodality therapy is of uncertain benefit, particularly in patients who have brain metastases at initial diagnosis.
185
What is the recommended management guideline for patients with advanced Germ Cell Tumor (GCT)?
All patients with advanced GCT should be treated for cure and referral to (or consultation with) experienced centers should be strongly considered.
186
What is the recommended chemotherapy treatment for patients with IGCCC good-prognosis disease?
For patients with IGCCC good-prognosis disease, three cycles of BEP is the preferred option.
187
For patients with IGCCC good-prognosis disease, three cycles of BEP is the preferred option.
For patients with IGCCC intermediate- and poor-risk disease, four cycles of BEP or VIP are both options.
188
How should tumor markers be managed during and after chemotherapy?
Tumor markers should be regularly monitored during and after chemotherapy.
189
What steps should be taken post-chemotherapy for all patients?
Post-chemotherapy, all patients should have biochemical and radiological re-staging to assess response and identify residual masses.
190
What is the recommended prophylaxis prior to the initiation of chemotherapy?
Prior to initiation of chemotherapy, prophylactic anticoagulation should be considered for patients at higher risk for VTE and a low risk for bleeding.
191
What is the guideline for prophylaxis during chemotherapy?
During chemotherapy, primary prophylaxis with G-CSF is required for patients receiving ifosfamide. It may be considered for patients with intermediate-/poor-risk disease or those at high risk based on age, comorbidities, and disease characteristics, or as secondary prophylaxis.
192
How should post-chemotherapy residual masses in NSGCT be managed?
In NSGCT, post-chemotherapy residual masses ≥1 cm and normal tumor markers should be resected.
193
What is the guideline for the management of post-chemotherapy residual masses <1 cm in NSGCT?
In NSGCT, post-chemotherapy residual masses <1 cm and normal tumor markers can be safely surveyed.
194
In NSGCT, post-chemotherapy residual masses <1 cm and normal tumor markers can be safely surveyed.
If surgery is performed for NSGCT retroperitoneal residual disease, in most cases, a full bilateral RPLND should be performed by experienced surgeons. It is acknowledged that more recent retrospective series have demonstrated low relapse rates in modified unilateral template surgery in select good-risk patients with ipsilateral primary landing-site disease <5 cm.
195
What considerations should be made when resecting residual disease?
In patients where a decision to resect residual disease is made, a low threshold to also resect residual disease outside of the retroperitoneum should be considered regardless of anatomic location because of the imperfect pathological concordance between sites.
196
What is the guideline for post-chemotherapy residual masses in seminoma?
Post-chemotherapy residual masses in seminoma are common.
197
What is the recommendation for seminoma residual masses ≤3 cm post-chemotherapy?
If they are ≤3 cm, PET scans are not recommended and the patient should be surveyed.
198
If they are ≤3 cm, PET scans are not recommended and the patient should be surveyed.
If they are >3 cm, a PET may be considered.
199
What is the guideline for negative PET scans in post-chemotherapy seminoma?
If the PET scan is negative, patients can be surveyed.
200
If the PET scan is negative, patients can be surveyed.
If the PET scan is positive, continued close observation is the preferred option.
201
What is the guideline for strongly positive PET scans over time in post-chemotherapy seminoma?
If the PET scan remains strongly positive over time, surgical resection or biopsy of the residual mass is the preferred option.
202
What is the guideline for growing post-chemotherapy residual masses in seminoma?
If the post-chemotherapy residual mass is growing on radiological imaging, surgical resection of the mass should be performed if technically feasible.
203
What is the guideline for further chemotherapy in patients with viable cancer cells in the specimen from post-chemotherapy residual mass resection?
The role of further chemotherapy in patients who have viable cancer cells in the pathological specimen from a post-chemotherapy residual mass resection is controversial. These cases require an individualized approach in an experienced center.
204
What is the recommended management for patients with brain metastases?
The management of patients with brain metastases is often multimodal and should be individualized and managed in an experienced center. VIP is the preferred option for first-line chemotherapy.
205
What factors influence the optimal treatment for relapsed Germ Cell Tumors (GCTs)?
The optimal treatment for relapsed GCTs depends on the initial treatment modality, the patient's response to prior therapy, the extent and timing of the relapse, and tumor histology.
206
Why is it critical to ensure that elevated tumor markers and/or radiological abnormalities during follow-up unquestionably represent relapsed GCT before initiating therapy?
Transient elevations in tumor markers might occur due to other causes, such as hypogonadism. Similarly, a slowly declining β-HCG post-primary chemotherapy may not indicate persistent disease, and new radiographical changes may not always represent relapsed disease (e.g., sarcoidosis). A complete picture, including clinical context, tumor markers, radiological imaging, and often biopsy, is necessary to confirm a diagnosis of relapse.
207
Give examples of scenarios where elevated tumor markers or radiological abnormalities might not represent a relapse of GCT.
Examples might include mild transient elevations of tumor markers from hypogonadism, a slowly declining β-HCG post-primary chemotherapy, and new radiographical changes from conditions like sarcoidosis.
208
What are the treatment options for patients on active surveillance who relapse in the retroperitoneum only?
The treatment options include locoregional therapy or standard cisplatin-based chemotherapy. Locoregional therapy includes radiotherapy for relapsed seminoma and retroperitoneal lymph node dissection (RPLND) for relapsed non-seminoma germ cell tumor (NSGCT).
209
What is the recommended treatment for patients on active surveillance who relapse at sites outside of the retroperitoneum?
The recommended treatment is standard first-line chemotherapy, as per the guideline's section "Treatment of advanced or metastatic disease."
210
For patients previously treated with locoregional therapy (radiation for stage I or II seminoma and primary RPLND for stage I and II NSGCT) who relapse, what is the recommended treatment?
The recommended treatment for these patients is chemotherapy, as per the guideline's section "Treatment of advanced or metastatic disease."
211
In Canada, what is the recommended approach for stage I germ cell tumors (GCT) post-orchiectomy?
Active surveillance is the recommended approach for stage I GCT post-orchiectomy in Canada, as the use of adjuvant chemotherapy is very uncommon.
212
What are the treatment options for patients with stage I seminoma who relapse after adjuvant carboplatin in the retroperitoneum only?
The treatment options for these patients include radiotherapy or chemotherapy. If they relapse with any sites outside of the retroperitoneum, curative-intent chemotherapy according to their International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group is recommended.
213
What treatments may be considered for patients with stage I non-seminomatous germ cell tumor (NSGCT) who relapse after adjuvant chemotherapy?
Treatment options for these patients may include retroperitoneal lymph node dissection (RPLND), standard chemotherapy (BEP/VIP), or salvage chemotherapy. The treatment choice will depend on factors such as the number of cycles of adjuvant cisplatin-based chemotherapy received, the timing and location of relapse, tumor marker elevation, and doubling time. RPLND alone is an option if the relapse is limited to the retroperitoneum and is marker-negative.
214
What is the recommended treatment for stage I seminoma patients who relapse with any sites outside of the retroperitoneum?
For these patients, curative-intent chemotherapy according to their IGCCCG prognostic group is recommended.
215
What are the seven variables identified by the International Prognostic Factors Study Group (IPFSG) associated with a favorable outcome after relapse in patients treated with cisplatin-based chemotherapy for advanced disease?
The seven variables are:
Seminoma histology
Gonadal primary
Response to primary therapy
Progression-free interval from primary therapy >6 months
AFP <1000 ug/L
HCG <1000 IU/L
Absence of bone/liver/brain metastases at relapse.
216
What are the two-year progression-free survival (PFS) and three-year overall survival (OS) rates for patients in the very low-risk category and the very high-risk category, according to the IPFSG?
For patients in the very low-risk category, the two-year PFS and three-year OS rates are 75% and 77%, respectively. For the very high-risk cohort, these rates decline to 5% and 6%, respectively.
217
What are the salvage treatment options for patients who relapse after cisplatin-based chemotherapy for advanced disease?
Salvage treatment options include further conventional-dose chemotherapy (CDCT) or high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT).
218
What does the ongoing TIGER trial aim to address?
The TIGER trial is designed to address which strategy is superior: salvage CDCT with paclitaxel, ifosfamide, and cisplatin (TIP) for four cycles, or paclitaxel and ifosfamide for two cycles, followed by three cycles of high-dose carboplatin and etoposide (TI-CE).
219
In the absence of solid, prospective data, what are the recommended treatments for patients in the IPFSG very low- or low-risk groups, and for patients in all other IPFSG risk categories?
For patients in the IPFSG very low- or low-risk groups, both CDCT or HDCT are reasonable options. For patients in all other IPFSG risk categories, HDCT is the preferred treatment option. There may be some circumstances where CDCT is a reasonable option in intermediate-risk patients.
220
What is the significance of successful upfront salvage therapy?
Successful upfront salvage therapy is imperative in terms of the likelihood of achieving a cure. HDCT in the first-line salvage setting appears more effective than in second-line or subsequent settings (two-year PFS 63% vs. 49%).
221
What is the preferred treatment option for patients who relapse with primary mediastinal GCT and would be classified as IPFSG very high-risk?
For these patients, HDCT would be the preferred option. In retrospective reviews, the long-term survival has ranged from 11–22%.
222
What is the prognostic score for patients who relapse after cisplatin-based first-line chemotherapy in testicular germ cell cancer?
The prognostic score is based on several parameters: primary site, prior response, progression-free interval, AFP and β-HCG levels at relapse, and metastasis to liver, brain, or bone. Each parameter is given a score from 0 to 3, which are summed to give a total score ranging from 0 to 10. This sum is then regrouped into categories, and the histology score points are added. The final prognostic score ranges from -1 (very low risk) to 3 (very high risk).
223
How are the points assigned based on the primary site in the prognostic score for testicular germ cell cancer?
The points are assigned as follows: Testis (0 points), Extragonadal (1 point), Mediastinal non-seminoma (2 points).
224
What are the scoring criteria based on prior response in the prognostic score for testicular germ cell cancer?
The points are assigned as follows: Complete remission or partial remission with negative markers (0 points), partial remission with positive markers or stable disease (1 point), progressive disease (2 points).
225
How is the progression-free interval considered in the prognostic score for testicular germ cell cancer?
If the progression-free interval is greater than 3 months, 0 points are assigned. If it's 3 months or less, 1 point is assigned.
226
How are AFP levels at relapse factored into the prognostic score for testicular germ cell cancer?
Normal AFP levels at relapse are assigned 0 points, levels up to 1000 ug/L are assigned 1 point, and levels above 1000 ug/L are assigned 2 points.
227
How are β-HCG levels at relapse factored into the prognostic score for testicular germ cell cancer?
β-HCG levels at relapse up to 1000 IU/L are assigned 0 points, and levels above 1000 IU/L are assigned 1 point.
228
How is metastasis to liver, brain, or bone factored into the prognostic score for testicular germ cell cancer?
If there's no metastasis to the liver, brain, or bone, 0 points are assigned. If there is, 1 point is assigned.
229
How is the final prognostic score derived for testicular germ cell cancer?
The final prognostic score is obtained by regrouping the sum of the points from the parameters (0 equals 0, 1 or 2 equals 1, 3 or 4 equals 2, 5 or more equals 3), and then adding the histology score points: pure seminoma subtracts 1 point, while non-seminoma or mixed tumors add 0 points. The final score ranges from -1 (very low risk) to 3 (very high risk).
230
What should salvage CDCT regimens for testicular germ cell cancer generally consist of?
Salvage CDCT regimens should consist of a three-drug regimen, generally with cisplatin plus ifosfamide as the backbone of therapy, plus either etoposide or paclitaxel.
231
Are there definitive randomized comparisons of salvage CDCT regimens for testicular germ cell cancer?
No, definitive randomized comparisons of salvage CDCT regimens are lacking.
232
What is the range of long-term disease control seen in patients on salvage CDCT regimens for testicular germ cell cancer?
Long-term disease control can be seen in 15–60% of patients but there is significant prognostic heterogeneity in these studies.
233
What is the implication of TIP having some of the highest disease control rates for testicular germ cell cancer?
Although TIP has some of the highest disease control rates published, these trials also included better prognostic patients (e.g., gonadal primary and cisplatin-responsive). Therefore, there is less certainty if the TIP regimen is as active in patients with worse prognostic features at relapse.
234
What should be offered to most patients with worse prognostic features at relapse?
Most of these patients should be offered HDCT.
235
If CDCT is chosen for a patient with testicular germ cell cancer, what is the preferred option in most cases?
If CDCT is chosen, TIPX4 is the preferred option in most cases.
236
Describe the importance of the setting in which HDCT with ASCT is performed.
HDCT with ASCT is a complex process that must be performed in experienced centers where there is adequate volume and expertise. This is to ensure the best supportive and pre/post-transplant care. It requires early close coordination between the transplant hematology and medical oncology teams to optimize survival outcomes.
237
What is the recommended treatment if HDCT is chosen for managing testicular germ cell cancer?
Two consecutive courses of high-dose carboplatin and etoposide followed by ASCT is the recommended treatment if HDCT is chosen.
238
In the context of HDCT and ASCT, is demonstration of cisplatin chemo-sensitivity a prerequisite?
No, being refractory to CDCT does not indicate one will be refractory to HDCT. Thus, demonstration of cisplatin chemo-sensitivity is not a prerequisite for planned HDCT.
239
What may some centers do to optimize the timing of salvage HDCT if required?
Some centers may have the capacity to collect stem cells from poor-risk patients during first-line chemotherapy. This is done to optimize the timing of salvage HDCT if required
240
Under what circumstances might CDCT salvage chemotherapy be required before HDCT and ASCT?
In some centers, one or two cycles of CDCT salvage chemotherapy (e.g., TIP) may be needed first to facilitate the organization of the transplant.
241
What is the recommended treatment for patients who relapse after salvage CDCT in the context of testicular germ cell cancer?
HDCT should be offered as it has been shown to be curative in some patients with second or subsequent relapses.
242
For patients who relapse after HDCT with ASCT or who are ineligible for this therapy, which chemotherapy agents might be considered?
Paclitaxel, gemcitabine, oxaliplatin, or combinations of these agents.
243
In the majority of patients who relapse after HDCT with ASCT or are ineligible for this therapy, what is the primary goal of the treatment?
Treatment is primarily palliative.
244
When chemotherapy (like paclitaxel, gemcitabine, oxaliplatin) is combined with subsequent surgical resection in patients who've relapsed after HDCT with ASCT or are ineligible for this therapy, what percentage of long-term survival has been reported?
10–15% long-term survival.
245
Can patients achieve long-term disease control or cure solely with aggressive local therapy, even if it's infrequent?
Yes, while infrequent, some patients may achieve long-term disease control or cure with aggressive local therapy.
246
What is the prognosis for patients relapsing with brain metastases in the context of testicular germ cell cancer?
The prognosis is generally poor. Factors influencing prognosis include the presence of liver or bone metastases and tumor marker levels.
247
In relapsing patients with testicular germ cell cancer and brain metastases, what is associated with improved survival?
Improved survival is associated with the use of multimodality therapy and high-dose chemotherapy (HDCT).
248
What should always be considered in relapsing testicular germ cell cancer patients with the intent of curative treatment?
The use of chemotherapy.
249
In the context of local therapy for brain metastases in testicular germ cell cancer, what are the possible interventions?
Local therapy may include surgery or radiation. However, these should not delay the initiation of chemotherapy.
250
What is the preferred radiation therapy for testicular germ cell cancer patients with brain metastases? Why?
If possible, stereotactic radiosurgery is preferred over whole-brain radiation to avoid long-term cognitive effects.
251
How strong is the data supporting the use of stereotactic radiosurgery in germ cell tumors (GCT)?
The data supporting its use in GCT is limited.
252
In the context of testicular germ cell cancer management, when should all residual masses be considered for post-chemotherapy surgical resection?
Residual masses should be considered for post-chemotherapy surgical resection in patients who normalize their markers with salvage chemotherapy (either CDCT or HDCT) but still have residual disease radiographically.
253
If a patient has viable disease after salvage chemotherapy and surgery, what is the consensus on further chemotherapy?
The role of further chemotherapy for patients with viable disease after salvage chemotherapy and surgery is unclear.
254
For patients with solitary sites of relapse, what might be the optimal treatment?
For some patients with solitary sites of relapse, surgical resection alone may be the optimal treatment.
255
When might patients be candidates for salvage or “desperation” surgery?
Patients who fail to normalize their markers or have progressive disease post-salvage systemic treatment may be candidates for salvage or “desperation” surgery, especially if all radiological disease can be resected.
256
What is the recommendation regarding the team and setting for performing "desperation" surgery?
"Desperation" surgery often requires a multidisciplinary surgical team and should be performed in experienced centers.
257
How is "late relapse" in the context of testicular germ cell cancer defined?
Late relapse is defined as disease recurrence more than two years after complete response to initial therapy.
258
What is the approximate risk of late relapse for seminoma patients?
The risk of late relapse is approximately 1.4% for seminoma patients.
259
How does the risk of late relapse for non-seminoma germ cell tumor (NSGCT) patients compare to seminoma patients?
The risk of late relapse is 3.2% for NSGCT patients, which is higher than seminoma patients.
260
What should one rule out when evaluating a potential late relapse?
One must rule out a new primary germ cell tumor (GCT) with metastases versus a late relapse. This can be done by performing a physical exam and an ultrasound of the contralateral testicle.
261
In the context of a late relapse, why is tissue confirmation important, especially when tumor markers are normal?
Tissue confirmation is crucial to rule out other possibilities like somatic transformation of teratoma or a new non-GCT malignancy.
262
Is the management of patients with late relapse straightforward or complex?
Management of patients with late relapse is complex and often multimodal.
263
Why is surgical resection emphasized in the management of late relapses?
Late relapses may have disease that is more chemo-resistant, making surgical resection an integral component of treatment.
264
When might chemotherapy still be required for patients with late relapse?
Chemotherapy may be needed pre- or postoperatively, depending on the site of relapse, tumor marker elevation, prior treatment, and the ability for complete resection.
265
What is the recommended follow-up duration for patients with late relapse of testicular germ cell cancer?
These patients require lifelong follow-up.
266
What is the consensus recommendation for all patients with relapsed GCT?
They should be treated for a cure. Referral to or consultation with experienced centers is strongly advised.
267
Before initiating therapy for relapsed GCT, what must be confirmed?
It's essential to ensure that elevated tumor markers and/or radiological abnormalities during followup genuinely represent relapsed GCT.
268
For stage I seminoma patients relapsing in the retroperitoneum while on surveillance, what are the treatment considerations?
They may qualify for radiation therapy if they fit the criteria for stage II seminoma recommendations; otherwise, chemotherapy based on the IGCCCG prognostic group is advised.
269
What is the treatment consideration for stage I seminoma patients who relapse in the retroperitoneum after adjuvant carboplatin?
Radiation therapy might be an option if they match the stage II seminoma criteria; otherwise, the IGCCCG prognostic group's chemotherapy is recommended.
270
How should stage I NSGCT patients relapsing in the retroperitoneum on surveillance be treated?
They should undergo curative-intent chemotherapy according to their IGCCCG prognostic group, with exceptions noted for certain stage I NSGCT patients.
271
What treatments are available for the rare cases of stage I NSGCT patients treated with adjuvant chemotherapy who relapse?
Treatment options include RPLND (for retroperitoneal relapses only), standard first-line chemotherapy, or salvage chemotherapy.
272
How should stage I patients relapsing outside the retroperitoneum be treated?
They should undergo curative-intent chemotherapy according to their IGCCCG prognostic group, with exceptions noted for certain stage I NSGCT patients.
273
What's the recommended treatment for stage I or II seminoma patients treated with radiation or stage I or II NSGCT patients treated with RPLND who subsequently relapse?
Chemotherapy should be administered based on the IGCCCG prognostic group.
274
For patients relapsing after initial cisplatin-based chemotherapy, what stratification should be employed for salvage chemotherapy?
Stratification should be based on the IPFSG criteria.
275
They should undergo curative-intent chemotherapy according to their IGCCCG prognostic group, with exceptions noted for certain stage I NSGCT patients.
Either CDCT or HDCT with ASCT are suitable choices.
276
What's crucial in the management of late relapses?
Late relapses necessitate multimodal therapy, and surgical resection of the disease is paramount.
277
For patients in the intermediate IPFSG risk group relapsing after initial cisplatin-based chemotherapy, what is the preferred treatment option?
HDCT with ASCT is the preferred option, though there may be circumstances where CDCT can be considered.
278
What is the suggested treatment for patients in the high and very high IPFSG risk groups who relapse after initial cisplatin-based chemotherapy?
HDCT with ASCT is the preferred treatment option.
279
If CDCT is chosen as the treatment option, which specific regimen is preferred?
TIPX4 is the preferred option.
280
When HDCT and ASCT are chosen as the treatment, what specific regimen is recommended?
Two consecutive courses of high-dose carboplatin and etoposide followed by tandem ASCT is the preferred choice
281
What treatment should be offered to patients who relapse after undergoing salvage CDCT?
HDCT with ASCT should be offered.
