Long-term multicentre experience of adjuvant radiotherapy for pN3 squamous cell carcinoma of the penis.

OBJECTIVE: To present the long-term adjuvant radiotherapy outcomes of patients with pN3 squamous cell carcinoma of the penis (SCCp) treated at two UK centres. PATIENTS AND METHODS: We conducted a retrospective audit of all pN3 SCCp patients, deemed suitable for adjuvant therapy by a specialist multidisciplinary team at St George's and Leeds Hospitals, who received adjuvant radiotherapy. Primary outcomes were recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Secondary outcomes were time to adjuvant treatment, frequency of in-field recurrence, site and side of recurrence, and dose and schedule of radiotherapy. RESULTS: A total of 146 patients were included: 121 completed radiotherapy, 4 did not complete radiotherapy and 21 did not start it. The median (interquartile range [IQR]) age was 59 (54-70)years. The 5-year RFS was 51%, CSS was 51% and OS was 44%. Adjuvant radiotherapy was started at a median (IQR) of 75 (48-106) days. A dose of 45 Gy in 20 fractions was most commonly used. Of the 125 patients who started adjuvant treatment, 55 relapsed. Of these relapses, 30 occurred in an inguinal or pelvic nodal station and 26 of the 30 were in a radiation field. Relapses in 18 of the 55 cases were in visceral sites only and seven were in both nodal (non-irradiated sites) and visceral sites. Doses of <50 Gy were used more commonly before 2013 and higher doses (>50 Gy) were more commonly used after 2013. CONCLUSIONS: Application of a standard radiotherapy protocol within a centralized supra-network setting has achieved survival outcomes that would appear better than those previously documented for either radiotherapy or chemotherapy in a cohort with solely pN3 disease. The addition of adjuvant chemotherapy may improve these outcomes further. These data suggest that adjuvant radiotherapy has a role to play in the management of men with pN3 SCCp.

Metastasis in penile corpus cavernosum from esophageal squamous carcinoma after curative resection: a case report.

BACKGROUND: Metastasis in penile corpus cavernosum from esophageal squamous carcinoma is a rare but fatal disease, which was reported in cases without series studies. CASE PRESENTATION: An 84-year-old male smoker, who had a history of curative resection of esophageal squamous carcinoma 12 months before, presented with aggressive dysuria and penis pain for 1 month. Ultrasonic guided biopsy diagnosed metastatic squamous carcinoma from the primary in the esophagus. The accurately modulated conformal radiotherapy and non-steroidal antiinflammatory drugs achieved to alleviate the penis pain temporarily. But the disease progressed and disseminated in a short period. He died of multiple metastases and cancer cachexia in 4 months. CONCLUSIONS: Primary esophageal cancer metastasis to penile corpus cavernosum refers to short onset time of metastasis, extensive dissemination, bad response to treatment and poor prognosis. Palliative therapy to patients with the disease could achieve temporary local symptom relief, but not prolong survival time. More research is necessary to understand the underlying mechanism of esophagheal metastasis.

High-Dose Rate Brachyther-apy in the Treatment of Early Stages of Penile Carcinoma.

BACKGROUND: Interstitial low dose rate brachyther-apy is established organ spar-ing treatment of T1- T2 penile carcinoma. Experience with high-dose rate brachyther-apy is limited in this indication. MATERIALS AND METHODS: Twenty-six patients with early penile carcinoma were treated by high-dose rate brachyther-apy at dose 18 × 3 Gy per fraction twice daily between 2002- 2018 at the Department of Oncology and Radiother-apy, University Hospital in Hradec Kralove. Breast interstitial brachyther-apy template was used for fixation and precise geometry reconstruction of stainless hollow needles. RESULTS: Median follow up was 85 months (range 7- 200 months). Acute reaction usually consisted of grade 2 mucositis that dissolved dur-ing 8 weeks after the treatment. Local recurrence occurred in 6 patients, 5 of them were successfully treated with partial amputation. One patient had a nodal recurrence successfully salvaged by lymphadenectomy. One patient developed necrosis of the glans requir-ing partial amputation. Currently, there are 24 patients alive without signs of dis-ease. One patient died of cardiac comorbidity, one died of duplicate lung cancer. Nineteen patients have a preserved penis (73%), 18 of them sexually active before treatment report satisfactory intercourse. CONCLUSION: Hyperfractionated interstitial high-dose rate brachyther-apy with 18 × 3 Gy per fraction twice daily is a promis-ing method in selected patients with penile carcinoma and deserves further evaluation in a larger prospective study. Key words penile neoplasms -  conservative treatment -  brachyther-apy This work was supported by programm Progres Q40. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 8. 1. 2019 Accepted: 15. 1. 2019.

Radiotherapy approaches for locally advanced penile cancer: neoadjuvant and adjuvant.

PURPOSE OF REVIEW: As penile cancer is an uncommon malignancy in the Western society, randomized trials to address the controversies in management have not previously been undertaken. The incorporation of multidisciplinary approaches in the management of advanced penile carcinoma has largely borrowed evidence from analogous malignancies in the anogenital region. This review is being undertaken in preparation for the international launch of InPACT, the International Penile Advanced Cancer Trial, a collaborative effort from European and North American trialists. RECENT FINDINGS: The literature supporting the development of this trial is reviewed, along with the trial design, goals, and endpoints. Level one evidence of the benefits of combined chemo-radiotherapy in the management of squamous cell carcinoma of the cervix, oropharynx, vulva, and anal canal has led to the introduction of this approach for advanced penile cancer. InPACT will compare chemo-radiotherapy to the traditional surgical approach, with or without neoadjuvant chemotherapy. SUMMARY: InPACT will define the roles and optimal sequencing of surgery, chemotherapy, and radiotherapy in advanced penile cancer. In the meantime, this collaborative effort among the major research consortiums of Europe and North America lends credibility to the application of this evidence to the penile site.

Organ-sparing treatment of penile cancer with interstitial pulsed-dose-rate brachytherapy.

AIM: To assess the efficacy and toxicity profile of protocol-based interstitial pulsed-dose-rate (PDR) brachytherapy for penile carcinoma. PATIENTS AND METHODS: From August 2002 to February 2014, 13 men with penile cancer were treated by interstitial brachytherapy. The tumor stage was T1 for eight patients, T2 for four patients, and T3 for one patient. The tumor grade was well differentiated for five patients and moderately differentiated for seven patients, while it was unknown for one patient. Lymph node staging was positive for three of 13 patients. All patients were treated using interstitial PDR brachytherapy with dose specifications according to the Paris system. For data collection of erectile dysfunction, the International Index of Erectile Function questionnaire was used, supplemented by the follow-up data. RESULTS: The median follow-up was 54.0 months (range, 13-155 months). Only one patient (1/13, 7.7 %) with local failure was documented. At 5 and 10 years, the local cumulative recurrence rate, disease-free survival, and the cancer-specific survival rates were 12.5 % (95 % CI, 80.4-119.6), 80.8 % (95 % CI, 75.2-124.8), and 77.9 % (95 % CI, 74.3-125.7), respectively. At the time of analysis, nine of 13 men were alive; two of 13 men died of distant metastases from the tumor and two for other reasons with no sign of cancer disease. Serious late side effects such as soft tissue necrosis occurred in four of 13 patients (30 %) and all were successfully treated with medication. Mutilating salvage surgery was not necessary in any of the cases. Urethral stenosis was documented for two of 13 (15.4 %) and dysuria occurred in four of 13 patients (30.8 %). Eight of 11 men (72.7 %) never or only sometimes had erectile dysfunction. CONCLUSION: In selected patients, interstitial PDR brachytherapy of penile cancer is effective as an organ-sparing treatment. It yields satisfactory results for the conservation of sexual function.

Erythroplasia of Queyrat treated by laser and light modalities: a systematic review.

Erythroplasia of Queyrat (EOQ) is a squamous cell carcinoma in situ most commonly located on the glans penis or prepuce. EOQ accounts for roughly 10 % of all penile malignancies and may lead to invasive squamous cell carcinoma. Standard therapy includes local excision, partial or total penectomy, cryotherapy, and topical cytotoxic agents. Treatment of EOQ has proven to be challenging due to low response rates and recurrence. In addition, radical procedures can significantly affect sexual function and quality of life. Alternative laser treatments and photodynamic therapy (PDT) offer promising results for treating EOQ. A systemic review of the literature was performed for articles discussing laser and light therapy for EOQ. Among the patients treated with the CO2 laser, 81.4 % of cases had complete remission after one session of treatment. Patients treated with PDT presented with more variable results, where 62.5 % of those treated with methyl aminolevulinate photodynamic therapy (MAL-PDT) achieved complete remission. Aminolevulinic acid (ALA-PDT) treatment showed a similar rate of remission at 58.3 %. One study utilized the Nd:YAG laser, which resulted in a recurrence of the lesion in four of the five patients treated. Of the methods reviewed, the CO2 laser offered the most promising results with a cosmetically excellent prognosis. Further studies with larger power and longer follow-up times are needed to determine the optimal treatment regimen for this penile malignancy.

External beam radiotherapy of extramammary Paget disease.

Extramammary Paget disease (EMPD) is an insidious intraepithelial neoplasm that is difficult to control with surgery, as large resections typically are required. An effective alternative is external beam radiotherapy (EBRT), which typically results in rapid resolution of EMPD. In this study, we analyzed long-term outcomes in 7 patients who were treated with EBRT for EMPD.

Dermo Beta Brachytherapy with 188Re in extramammary Paget's disease.

AIM: Extramammary Paget's disease (EMPD) is a rare neoplastic pathology involving the vulva, scrotum, and perianal areas, and it is characterized by a slow and insidious course. EMPD may also be associated with internal malignancy, and its clinical presentation features long-standing pruritic lesions, eczema-like, refractory to any therapy. The pathogenesis is unclear, and univocal standardization of treatment is yet to be determined. As regard to the patients who suffer from it, women are more often affected than men. The therapeutic approach depends on the extent of involvement; wide surgical excision is the first choice among treatments, but other forms of therapy, alone or in combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as external beam radiotherapy and Brachytherapy. In the present paper a new therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re. METHODS: Five patients with EMPD, one secondary and four primary cases, have been treated by Brachytherapy with DBBT. This therapy has been successfully used for non-melanocytic skin tumors and basically consists in the topical application of a specially designed, tailor-made mould containing a radioactive beta-emitting isotope, rhenium-188. RESULTS: The patients healed completely, after one session in one case and after two sessions in four cases, with 34 months mean follow-up. CONCLUSION: Brachyterapy could represent a new alternative therapy, instead than invasive treatments as surgery and conventional radiotherapy, capable to treat EMPD independently of its extension, with aesthetic and functional satisfactory results.

A Technique to Deliver Conformal External Beam Radiation for Squamous Carcinoma of the Penile Glans and Urethra.

This study presents an approach to external beam radiation therapy for treating penile cancer using a small water bath. This modified technique involves the use of an acrylic, cuboid-shaped water bath with dimensions 6 × 6 × 8 cm3. The water bath is filled with readily available saline solution maintained at room temperature. The patient is positioned in the prone position, and the penis is placed within the water bath. The isocenter is set at the center of the water bath, and bilateral beams are positioned at 89.1° and 270.9°. The proposed technique was evaluated based on dose calculations, demonstrating a clinical target volume dose with a Dmax of 103.5% and a Dmin of 100.0% of the prescribed dose. Additionally, the method showed a low organs-at-risk dose, with a Dmean of only 1% for the testicles. The treatment zone inside the water bath also showed a uniform dose distribution. This technique not only offers high treatment efficiency and more accurate dose distribution to the targeted area but also provides additional benefits, including reduced toxicity to organs at risk and increased device utilization efficiency. In conclusion, the proposed modified external beam radiation therapy method presents a promising alternative for patients with penile cancer, enhancing treatment precision and safety.

Next-generation sequencing of primary testicular lymphoma and relapse in the glans penis after prophylactic radiation therapy: a rare case report.

BACKGROUND: Primary testicular lymphoma (PTL) is relatively rare. The contralateral testis is a common site of PTL relapse; therefore, once complete remission is achieved, radiation therapy (RT) is administered to the contralateral testis to prevent relapse. CASE PRESENTATION: A 76-year-old man was diagnosed with PTL and received RT as described above. However, despite achieving and maintaining complete remission, a mass diagnosed as diffuse large B-cell lymphoma by tissue biopsy developed in the glans penis 6.5 years after prophylactic RT. We investigated whether the glans penile lymphoma was PTL relapse or a new malignancy by genomic analysis using next-generation sequencing of DNA extracted from two histopathological specimens. CONCLUSIONS: We found the same variant allele fraction in four somatic genes (MYD88, IL7R, BLNK, and FLT3) at similar frequencies, indicating that the glans penile lymphoma had the same origin as the PTL. To the best of our knowledge, this is the first case report of PTL relapse in the glans penis.

Optimizing Target Volume for Adjuvant Radiation Therapy in Penile Cancer.

PURPOSE: Recent studies have reported improved outcomes with adjuvant radiation therapy in penile cancer. However, the appropriate target volumes to be irradiated in this group of patients for optimal outcomes are still unclear. This study aims to report the patterns of failure and define target volumes to be irradiated in patients with pN3 penile cancer. METHODS AND MATERIALS: Patients with pT1-T4, pN3, cM0, and squamous cell carcinoma of the penis who received adjuvant radiation therapy (involved field or extended field), with or without concurrent chemotherapy were included in the study. Complete information on disease characteristics, radiation therapy target details, and patterns of failure were available for 75 patients. Disease-free (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and log-rank test was used to compare survival outcomes between the involved field and extended field radiation therapy groups. Multivariate analysis was performed using the Cox proportional hazards model to analyze factors correlating with survival outcomes. RESULTS: At a median follow-up of 39 months, 38.6% (29/75) of patients had relapsed either locally, regionally, or at distant sites. Of the 24 patients who received extended field radiation therapy (EFRT), only 1 (4%) patient experienced relapse. Twenty-eight (55%) patients experienced relapse after involved-field radiation therapy (IFRT), of which 28.5% were regional-only relapses and 64% relapses were associated with a regional component. The 2-year DFS and OS of the entire cohort were 62.2% and 70.8%, respectively. The 2-year DFS was 67.9% in patients who received IFRT and 94.1% in those who received EFRT (P = .002), and the 2-year OS was 62.4% with IFRT and 91.1% with EFRT (P = .014). Extended field radiation therapy was associated with an improved DFS (hazard ratio, 12.2; 95% confidence interval, 1.5-97.4; P = .02) and OS (hazard ratio, 4.6; 95% confidence interval, 1-21.5; P = .05) on multivariate analysis. CONCLUSIONS: Extended field radiation therapy significantly improves clinical outcomes compared with involved-field radiation in patients with pN3 penile cancer.

Organ sparing treatment for penile cancer using a 3D-printed high-dose-rate brachytherapy applicator.

PURPOSE: We present a case study of the treatment of localized squamous cell carcinoma on the glans penis with a custom-fabricated high-dose-rate (HDR) brachytherapy applicator. METHODS AND MATERIALS: A cylindrically shaped applicator was fabricated with eight embedded channels suitable for standard plastic brachytherapy catheters. An additional custom silicone bolus/sleeve was designed to be used with the 3D-printed applicator to provide an additional offset from the source to skin to reduce the surface dose and for patient comfort. RESULTS: The patient (recurrent cT1a penile cancer) underwent CT simulation, and the brachytherapy plan was created with a nominal prescription dose of 40 Gy in 10 fractions given bidaily to the surface, and 35 Gy at 5 mm depth. Dose coverage to the clinical target volume was 94% (D90). Most fractions were treated with only 5-10 min of setup time. Follow up visits up to 1 year showed no evidence of disease with no significant changes in urinary and sexual function and limited cosmetic detriment to the patient. CONCLUSIONS: Patient-specific organ-sparing HDR plesiotherapy using 3D printing technology can provide reliable and reproducible patient setup and may be effective in achieving disease control for superficial penile cancer, although preserving patient quality of life.

Atezolizumab With or Without Radiotherapy for Advanced Squamous Cell Carcinoma of the Penis (The PERICLES Study): A Phase II Trial.

PURPOSE: Patients with advanced penile squamous cell carcinoma have a poor prognosis (21% 2-year overall survival [OS] from diagnosis). We assessed the activity of atezolizumab (anti-PD-L1) in patients with advanced penile cancer, with or without radiotherapy (RT). PATIENTS AND METHODS: A single-center, nonrandomized phase II study with two treatment arms was conducted in 32 patients with histologically confirmed advanced penile cancer. All patients received atezolizumab (1,200 mg) once every 3 weeks. Twenty patients, who were expected to benefit from RT for locoregional disease control, received additional irradiation. The primary end point was 1-year progression-free survival (PFS) for the complete cohort and was reached if the actual 1-year PFS was at least 35%. Secondary end points included OS, objective response rate (ORR), and tolerability. Exploratory biomarker analyses were conducted in pretreatment specimens. RESULTS: Median follow-up was 29.1 months (IQR, 18.1-33.5). Grade 3-4 adverse events related to atezolizumab or RT were observed in 3/32 (9.4%) and 13/20 (65%) patients, respectively. One-year PFS was 12.5% (95% CI, 5.0 to 31.3), which did not meet the study's primary end point. Median OS was 11.3 months (95% CI, 5.5 to 18.7). In the objective response-evaluable population (n = 30; 93.8%), the ORR was 16.7% (95% CI, 6 to 35), including 2 (6.7%) complete responders and 3 (10%) partial responders. Improved PFS was observed in patients with high-risk human papillomavirus (hrHPV)-positive tumors (P = .003) and those with high infiltration of intratumoral CD3+CD8+ T cells (P = .037). CONCLUSION: Although the primary end point of 1-year PFS was not met, durable antitumor activity to atezolizumab was observed in a subset of patients. Biomarkers, such as hrHPV and intratumoral CD3+CD8+ T-cell infiltration, may help to better select responders.

Surgery and radiation therapy for extramedullary plasmacytoma of the penile mucosa in a dog.

A 10-year-old neutered male Italian greyhound dog was presented because it had a penile plasmacytoma. Surgery followed by radiation therapy resulted in local control and survival for 1688 days. This is the first report of surgery and definitive radiation therapy for curative intent therapy of extramedullary penile plasmacytoma in a dog.A 10-year-old neutered male Italian greyhound dog was presented because it had a penile plasmacytoma. Surgery followed by radiation therapy resulted in local control and survival for 1688 days. This is the first report of surgery and definitive radiation therapy for curative intent therapy of extramedullary penile plasmacytoma in a dog.

RésuméPlasmocytome extramédullaire du pénis traité avec chirurgie et radiothérapie chez un chien. Un chien petit lévrier italien mâle castré âgé de 10 ans fut présenté suite à un diagnostic de plasmocytome extramédullaire du pénis. La chirurgie, suivie d'une radiothérapie, permit un contrôle local et une survie de plus de 1688 jours. Il s'agit du premier cas rapporté de plasmocytome extramédullaire du pénis chez un chien traité en plurimodalité avec chirurgie et radiothérapie définitive.(Traduit par les auteurs).

Organ preserving radiation strategies for penile cancer.

INTRODUCTION: The majorities of penile cancers are of squamous cell origin and thus are amenable to treatment and cure by radiation. Despite the move toward penile sparing strategies, radiation remains an under-utilized and often neglected option. This paper will review the various radio-therapeutic approaches for penile cancer and the literature supporting their use. English, French and Spanish literature on penile cancer was reviewed for the past 5 decades and classified according to modality: external beam radiotherapy, interstitial brachytherapy and surface mold brachytherapy. Many series span several decades and include a wide range of stages, especially for external beam radiotherapy. Penile preservation obviously will depend on dose prescription and stage at treatment. Nonetheless, in general, penile sparing with external beam ranges from 36% to 66% at 5 years. For the selected patients appropriate for interstitial brachytherapy penile sparing is 77% to 87% at 5 years, decreasing to 70% at 10 years. Mold therapy is selected for those with very superficial disease and penile sparing is consequently higher. CONCLUSIONS: The development of centers of excellence for the management of this uncommon disease is encouraged. The required surgical and radiotherapy skill sets cannot be expected to be available in all centers. A multidisciplinary evaluation of each patient will facilitate selection of optimal management from the outset.

Radiotherapy for penile cancers.

Penile cancers are uncommon and should be treated in expert center. Radiotherapy indications are mainly limited to exclusive brachytherapy for early stage penile glans cancer. Brachytherapy yields to excellent outcome for disease control and organ and function preservation. Only scarce data are available for external beam radiation therapy. It could be considered as palliative setting for irradiation of the primary tumor. For lymph node irradiation, external beam radiation therapy (with or without chemotherapy) could be discussed either as neoadjuvant approach prior to surgery for massive inguinal lymph node invasion or as adjuvant approach in case of high-risk of relapse. However, these cases should be discussed on an individual basis, as the level of evidence is poor. We present the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for penile glans cancer.

Novel portable apparatus for outpatient high-dose-rate (HDR) brachytherapy in penile cancer.

BACKGROUND: Penile squamous cell carcinoma (PSC) is traditionally treated with surgical resection with significant morbidity. Penile sparing approaches, such as brachytherapy, require expertise, prolonged inpatient stays, poor patient convenience, and heterogenous plans with variable long-term toxicity. In this study, we describe the protocol for novel portable apparatus created for PSC, allowing outpatient hybrid interstitial/surface brachytherapy, improving homogeneity and patient convenience. METHODS: A portable brachytherapy apparatus was developed utilizing a foley catheter, prostate template, 6F interstitial catheters, 5 mm bolus, and a jock strap. The apparatus allowed for internal and external catheter placement housed in a jock strap to allow mobility and defecation without affecting the implant. High-dose-rate brachytherapy was performed as an outpatient. RESULTS: The apparatus was then used on a 62-year-old male with cT2pN0M0 (stage IIA) PSC with bilateral glans and urethral meatus involvement, who elected for definitive brachytherapy (4000cGy in 10 fractions over 5-days). Given external dwell positions, heterogeneity correction of the template was calculated (AAPM TG186) with <2% variation. Patient had minimal impact on his active lifestyle during treatment and had complete clinical response at 3-months. Grade 2 skin desquamation resolved at 2-months, with no necrosis. At 6-months, he was able to resume sexual intercourse, and at 12-months, he remained disease-free with sexual and urinary function intact. CONCLUSIONS: Novel portable implant allows for improved patient convenience, reduced inpatient stay, capable of optimizing dosimetry with hybrid brachytherapy. This outpatient treatment allows the opportunity to increase fractionation, offering high local-control and lower toxicity. Future studies utilizing this apparatus for more fractionated regimens with further lower dose-per-fraction (∼3 Gy/fraction) is recommended.

Radiotherapy for node positive penile cancer: experience of the Leeds teaching hospitals.

PURPOSE: We studied the outcomes in patients with node positive penile cancer who received radiotherapy to inguinal and pelvic nodes. Although half of node positive cases are cured by lymphadenectomy, little data are available on the potential further benefits and toxicities of postoperative radiotherapy. MATERIALS AND METHODS: We retrospectively audited the clinical notes and electronic records of 23 patients referred to a specialist center from 2002 to 2008 who received radiotherapy to the inguinal/pelvic nodes as adjuvant treatment after lymphadenectomy (14), or as high grade palliation for extensive/fixed nodes (8) or extensive local tumor (1). The primary outcome measure was overall survival. Secondary end points were locoregional recurrence-free survival and toxicity. RESULTS: All 13 deaths were due to penile cancer. Patients with adjuvant therapy had better overall survival (66% vs 11%, p<0.001) and locoregional relapse-free survival (56% vs 22%, p=0.03) than those with high grade palliation. Six of 14 adjuvant cases and 7 of 9 with high grade palliation relapsed locoregionally. Of patients with adjuvant therapy and extracapsular spread 1 of 6 with N1, 1 of 4 with N2 and 3 of 4 with N3 disease relapsed (p=0.31). No life threatening toxicity was observed. It was difficult to determine the relative contributions of radiotherapy and surgery to leg/scrotal lymphedema. The study was limited by its small size, which reflects the rarity of this tumor. CONCLUSIONS: Adjuvant radiotherapy appears to have a role after inguinal lymphadenectomy, particularly in patients with extracapsular nodal spread, in whom historically survival rates have been poor. Our findings warrant further investigation in larger series of patients.