Lymph Nodes
Summary of Evidence and Guidelines for rILND in cN1–2 Disease
Summary of evidence
Open radical ILND is the standard for cN1–2 disease. (, 2a)
2559625
rILND carries a significant risk of complications (21–55%). (, 2a)
2559625
A single study reported on fsILND, fascial-sparing ILND has been reported (single study) and in cN1–2 disease which appears to offer similar oncological outcomes, and reduced complications. (, 2b)
2559625
Lymph node yield and lymph node dissection (LND) appear related to survival, however, variance in accepted values, pathological assessment, and stage migration prevent recommendation of a specific LN count. (, 2a)
2559625
Delay in nodal management of more than 3–6 months may affect disease-free survival (DFS). (, 3)
2559625
Minimally-invasive approaches for ILND (video endoscopic inguinal lymph node dissection [VEIL]/robot-assisted video-endoscopic inguinal pelvic lymph node dissection [RAVEIL]) generally have longer operative times, equivalent LN yields, shorter length of hospital stay and lower wound complications when compared with open ILND. However, since current evidence is very limited in cN1–2 patients, no recommendation for minimally-invasive approaches can be provided. (, 2b)
2559625
Recommendations
In patients with cN1 disease offer either ipsilateral:
- Fascial-sparing inguinal lymph node dissection
- Open radical ILND; sparing the saphenous vein, if possible
(S, )2559625
In patients with cN2 disease offer ipsilateral open radical ILND; sparing the saphenous vein, if possible. (S, )
2559625
Offer minimally-invasive inguinal LN dissection to patients with cN1–2 disease only as part of a clinical trial. (S, )
2559625
Offer chemotherapy as an alternative approach to upfront surgery in selected patients with bulky mobile inguinal nodes or bilateral disease (cN2) who are candidates for cisplatin and taxane-based chemotherapy (see page 18). (W, )
2559625
Complete surgical inguinal and pelvic nodal management within 3 months of diagnosis (unless the patient has undergone prior neoadjuvant chemotherapy). (W, )
2559625
Summary of Evidence and Guidelines for Prophylactic Pelvic Lymph Node Dissection
Summary of evidence
Prophylactic pelvic lymph node dissection (PLND) in most cases represents a staging procedure that can thus identify candidates for early adjuvant therapy, although in select patients it may also provide a therapeutic benefit. (, 3)
2559625
Three or more positive inguinal nodes or ENE of cancer in inguinal nodes are associated with a significantly higher incidence of pelvic LN metastases. (, 3)
2559625
Recommendations
Offer open or minimally-invasive prophylactic ipsilateral pelvic lymphadenectomy to patients if:
- Three or more inguinal nodes are involved on one side on pathological examination
- ENE is reported on pathological examination
(W, )2559625
Complete surgical inguinal and pelvic nodal management within 3 months of diagnosis (unless the patient has undergone neoadjuvant chemotherapy). (W, )
2559625
Summary of Evidence and Guidelines for the Surgical Management of cN3 Disease
Summary of evidence
Surgery alone will rarely cure patients with cN3 disease. (, 3)
2559625
Even when technically feasible, upfront surgery is associated with significant complications which may delay or prevent delivery of adjuvant therapy. (, 3)
2559625
About half of the patients with advanced (cN2–cN3) penile cancer respond to combination chemotherapy. Responders that subsequently undergo consolidative inguinal/pelvic LND have an overall survival (OS) chance of about 50% at 5 years. (, 2a)
2559625
Inguinal LND in cN3 patients often requires resection of overlying skin to effectively remove a fixed bulky nodal mass. (, 4)
2559625
The available literature includes virtually no cN3 patients to assess the efficacy or safety of minimally-invasive ILND. (, 4)
2559625
Recommendations
Offer neoadjuvant chemotherapy (NAC) using a cisplatin- and taxane-based combination to chemotherapy-fit patients with pelvic LN involvement or those with extensive inguinal involvement (cN3), in preference to up front surgery (see page 18). (W, )
2559625
Offer surgery to patients responding to NAC in whom resection is feasible. (S, )
2559625
Offer surgery to patients who have not progressed during NAC, but resection is feasible. See also (chemo)radiation. (W, )
2559625
Do not offer video endoscopic inguinal lymphadenectomy. (S, )
2559625
Summary of Evidence and Guidelines for Neoadjuvant and Adjuvant Chemotherapy
Summary of evidence
Results support the activity of NAC in patients with clinically involved regional LNs from penile SCC. However, randomized studies are lacking, and substantial concerns remain regarding the selection of patients who are best suited for a systemic therapy approach upfront. (, 2b)
2559625
The available evidence favours a cisplatin- and taxane-based combination (doublet or triplet) as the preferred approach. (, 2b)
2559625
Limited data support the use of adjuvant chemotherapy to improve OS following surgical resection. However, it could be offered to patients with pN3 disease post-LND if NAC has not been received, upon careful consideration of risks and benefits with the patient. (, 4)
2559625
Recommendations
Offer neoadjuvant chemotherapy using a cisplatin- and taxane-based combination to chemotherapy-fit patients with pelvic lymph node involvement or those with extensive inguinal involvement (cN3), in preference to up front surgery. (W, )
2559625
Offer chemotherapy as an alternative approach to upfront surgery to selected patients with bulky mobile inguinal nodes or bilateral disease (cN2) who are candidates for cisplatin and taxane-based chemotherapy. (W, )
2559625
Have a balanced discussion of risks and benefits of adjuvant chemotherapy with high-risk patients with surgically resected disease, in particular with those with pathological pelvic LN involvement (pN3) (see page 19). (W, )
2559625
Summary of Evidence and Guidelines for Pre- and Post-Operative Radiotherapy
Summary of evidence
Adjuvant radiotherapy results in increased OS if greater than two inguinal LN-positive and PLND-dissection negative. (, 2b)
2559625
Adjuvant conventional radiotherapy doses are often insufficient for durable control. Increased DSS and recurrence-free survival (RFS) in penile cancer requires 54 gray (Gy) for ENE and 57–60 Gy for positive margins. (, 3)
2559625
Peri-operative chemo-radiation
Chemo-radiation significantly improves loco-regional control over radiotherapy alone for other SCC originating in anal canal or head and neck, whilst in vulvar cancers it improves OS. The evidence is, however, sparse in penile cancer. (, 1b)
2559625
Recommendations
Offer adjuvant radiotherapy (with or without chemo sensitisation) to patients with pN2/N3 disease, including those who received prior neoadjuvant chemotherapy. (W, )
2559625
Offer definitive radiotherapy (with or without chemo sensitisation) to patients unwilling or unable to undergo surgery for lymph node dissection. (W, )
2559625
Offer radiotherapy (with or without chemo sensitisation) to cN3 patients who are not candidates for multi-agent chemotherapy. (W, )
2559625
Systemic and Palliative Therapies for Advanced Disease
Summary of Evidence and Guidelines for Systemic and Palliative Therapies for Advanced Penile Cancer
Summary of evidence
Low-level data support the use of platinum-based chemotherapy as first-line systemic therapy in advanced disease. (, 3)
2559625
Effective second-line palliative chemotherapy regimens are lacking. Secondline chemotherapy in multiple studies was associated with median OS of 6 months or less. (, 3)
2559625
Initial phase II or basket studies assessed anti-epidermal growth factor receptor (EGFR) therapy or checkpoint inhibition, as monotherapy or combination therapy, in advanced disease. Early evidence of promising clinical activity has been reported in patients with penile cancer. (, 2b)
2559625
Recommendations
Systemic therapies
Offer patients with distant metastatic disease, platinum-based chemotherapy as the preferred approach to first-line palliative systemic therapy. (W, )
2559625
Do not offer bleomycin because of the pulmonary toxicity risk. (S, )
2559625
Offer patients with progressive disease under platinum chemotherapy the opportunity to enroll in clinical trials, including experimental therapies within phase I or basket trials. (S, )
2559625
Radiotherapy
Offer radiotherapy for symptom control (palliation) in advanced disease. (S, )
2559625
Follow-Up and Quality of Life (QoL)
Summary of Evidence and Guidelines for Follow-up and QoL
Summary of evidence
Follow-up surveillance is important as early detection of recurrence may increase the likelihood of curative treatment. (, 3)
2559625
Local or regional nodal recurrences usually occur within two years of primary treatment. (, 3)
2559625
Penile cancer has a significant impact on QoL in many ways and there remain many unmet needs to address. (, 4)
2559625
There is very little data on QoL after treatment for penile cancer. In particular, there is heterogeneity of the psychometric tools used to assess QoL outcomes and further research is needed to develop disease-specific patient reported outcome measures (PROMS) for penile cancer. (, 3)
2559625
Generally, penile-preserving surgery preserves erectile function, although glans sensation and orgasm can be affected. Overall, partial penectomy is associated with poorer sexual outcomes. (, 2b)
2559625
Access to psychological support, counselling and psychosexual therapy are critical components of a holistic and multi-disciplinary patient support service. (, 4)
2559625
Ideally, following nodal surgery, patients would be referred to specialist lymphoedema services for assessment and management before any significant lymphoedema occurs. (, 4)
2559625
In one United Kingdom (UK) specialist penile cancer centre (referral population approximately 11 million), 5-year CSS rates were observed to improve by up to 12% to 85% following centralisation. (, 3)
2559625
Recommendations
Deliver penile cancer care as part of an extended multi-disciplinary team comprising of urologists specialising in penile cancer, specialist nurses, pathologists, uro-radiologists, nuclear medicine specialists, medical and radiation oncologists, lymphoedema therapists, psychologists, counsellors, palliative care teams for early symptom control, reconstructive surgeons, vascular surgeons, sex therapists. (S, )
2559625
Follow-up men after penile cancer treatment, initially three-monthly for 2 years then less frequently to assess for recurrent disease and to offer patient support services through the extended multi-disciplinary team. At discharge, recommend self-examination with easy access back to the clinic as local recurrence can occur late. (S, )
2559625
Discuss the psychological impact of penile cancer and its treatments with the patient and offer psychological support and counselling services. (S, )
2559625
Discuss the negative impact of treatments for the primary tumour on penile appearance, sensation, urinary and sexual function so that the patient is better prepared for the challenges he may face. (S, )
2559625
Discuss the potential impact of lymphoedema as a consequence of inguinal and pelvic lymph node treatment with the patient and assess patients for it at follow-up and refer to lymphoedema therapists early. (S, )
2559625